Hendryx is known for her work as a solo artist as well as for being one-third of the trio Labelle, who had a hit with "Lady Marmalade." Her music has ranged from soul, funk, and R&B to hard rock, new wave, and new-age. She stated in an interview that her family's last name was originally spelled with an "i" and that she was a distant cousin of American musician Jimi Hendrix.[4]

Hendryx was born in Trenton, New Jersey in 1944 where she met fellow New Jersey native Sarah Dash and later met Philadelphia-born singer Patricia Holte (Patti LaBelle). After a short-lived tenure as a member of the Del-Capris, Hendryx and Dash formed a singing group with Holte (once the lead singer of a girl group in Philadelphia called The Ordettes). In 1961, Cindy Birdsong, from Camden, New Jersey, became the fourth member of the group, who became the 'Bluebelles' and signed their first deal with Newtown Records.

After the release of their debut hit, 1962's "I Sold My Heart to the Junkman", their name altered again to Patti LaBelle and the Bluebelles. Hendryx's husky alto differed from Dash's sharp soprano, LaBelle's mezzo-soprano and Birdsong's second soprano. During this tenure, the group became known for their emotional live performances and their renditions of classic standards such as "You'll Never Walk Alone", "Over The Rainbow"and "Danny Boy". The group often found themselves competing against girl groups such as The Chantels, Shirelles and The Supremes. In 1967, Hendryx, LaBelle and Dash were shocked to discover that Birdsong had secretly joined the Supremes after Florence Ballard was ousted from the group by Motown. Different members of the group were in touch with Birdsong over the years. Birdsong's relationships with the Bluebelles healed and they came together again for the ceremony when the group won an R&B Foundation Lifetime Achievement Award in 1999.

For the next three years, the group struggled to compete against the changing musical landscape for which their girl group sound had fallen out of favor with popular audiences. In 1971, they moved to England, where they had a cult fan base, and on the advice of Vicki Wickham, changed their name to Labelle and ditched the dresses and bouffant wigs for jeans and Afros. Releasing transitional albums including 1971's Labelle and 1972's Moon Shadow, the group recorded material that included sexual and political subject matter – unheard of for an all-female black group. The transition was hard for lead singer LaBelle, who was a fan of the group's early-era ballads, but she eventually gave in. Member Dash remained neutral throughout the tenure of the group. Shortly after releasing Labelle, the group became the opening act for The Who, whose producer Kit Lambert had produced the group's Warner debut. They also opened for Laura Nyro during that same time and sang backup on her album, Gonna Take a Miracle.

After the release of Moon Shadow, Hendryx became the chief songwriter for most of the group's records while LaBelle and Dash occasionally wrote their own material. After successfully opening for The Rolling Stones during the group's American tour in 1973, the group released Pressure Cookin', where they once again adopted a new look as "glam rock, space-age divas". As a songwriter Hendryx subsequently wrote powerful ballads ("You Turn Me On" and "Nightbird" from Nightbirds, "Going Down Makes Me Shiver" from Labelle's final album, Chameleon), and a wealth of more uptempo numbers ("Space Children," "Messin' With My Mind," "Gypsy Moths," and "Who's Watching the Watcher"). Her themes were unconventional, diverse, and often experimental. Her composition "A Man In A Trenchcoat (Voodoo)" from Chameleon also marked Hendryx's first time singing lead vocal on an album. In 1974, the group hit gold with the release of Nightbirds following the release of the smash hit, "Lady Marmalade". In her memoir Don't Block The Blessings, Labelle frontwoman Patti LaBelle attributed the band's 1976 breakup to musical and personal tensions within the group. Labelle, Dash, and Hendryx all embarked on solo careers; Wickham stayed on with Hendryx to manage her solo career.

In 1977, Hendryx released her first solo album, a self-titled collection. A blend of soul and hard rock, it contained notable tracks such as "Winning" (later recorded by Santana) and the ballad "Leaving Here Today". It quickly disappeared from the shelves, and Hendryx was dropped from Epic. Subsequently, she recorded four singles for Arista (London), which also escaped chart success. She did find success doing session work during this period, most notably providing background vocals for Talking Heads and touring with them, appearing first at the major Heatwave festival in August 1980. She contributed the song "Checkmate" on Dusty Springfield's album It Begins Again in 1978 (the first of Springfield's multiple comeback attempts).

In the early 1980s, Hendryx fronted her own progressive art rock group, Zero Cool, which included guitarist Naux (China Shop, Richard Hell), bassist Michael Allison (Darshan Ambient), guitarist Kevin Fullen and drummer Jimmy Allington. Simultaneously, she sang with experimental funk group Material, achieving a giant club hit with "Busting Out." She had two other major club hits soon after: a dance remake of The Supremes' "Love Is Like An Itching In My Heart," and, in a lead vocal guest spot for the Cage, "Do What You Wanna Do." Material also produced her second album, Nona, in 1983. The hip, contemporary dance sound of this album proved to be more charts-compatible, with the disco music times, and the single "Keep It Confidential" becoming a modest R&B hit, and a remix of "B-boys" finding major success on the dance charts. "Transformation" became a Hendryx staple, and was later covered by Fierce Ruling Diva. Another particularly noteworthy track on the album is the ballad "Design For Living," which featured guests Laurie Anderson, Gina Shock of The Go-Go's, Valerie Simpson of Ashford & Simpson, Tina Weymouth of Tom Tom Club and Talking Heads, Nancy Wilson of Heart, and former bandmate Patti LaBelle.

In the mid-1980s, Hendryx was recruited by RCA to record songs for various soundtracks, including: the theme for Moving Violations; "I Sweat (Going Through the Motions)," a commercial hit for Hendryx from the Jamie Lee Curtis film Perfect; and "Transparent" from the Eddie Murphy vehicle, Coming To America. Her album The Art Of Defense was released in 1984.

In 1985, Hendryx wrote and recorded "Rock This House" with Keith Richards, from her album The Heat. The song was nominated for a Grammy Award. The same year, the MTV broadcast of the video "I Need Love" stirred some controversy for featuring drag queens. As a result, it was quickly removed from MTV's playlist.

Hendryx took a detour from commercial music with Skin Diver, a new age record produced with long-time Tangerine Dream member Peter Baumann. The album was generally greeted with positive feedback from critics, but was commercially unsuccessful. The title track did attract some attention, as did "Women Who Fly", which was later covered by Jefferson Starship.

In addition to the duet-album You Have to Cry Sometime with Billy Vera and a couple of compilation-only tracks, Hendryx has recorded more than five albums worth of music, but she has been unable to release any of it due to lack of interest from major and independent record labels. Her Epic, RCA and EMI albums have long been out of print and have only recently attracted the attention of specialist reissue labels, but a Best Of album titled Transformation was released in 1999 by Razor & Tie. Her 1977 debut solo album was issued for the first time on CD by the T-Bird imprint of the UK reissue label Cherry Red in the fall of 2010. UK R&B reissue label Funky Town Grooves released The Heat on CD in late 2011, which included three bonus tracks. Funky Town Grooves announced plans to release both Nona and The Art of Defense in early 2012.[citation needed] Each CD is to include seven bonus tracks.

Hendryx has also dabbled in acting. She wrote and performed the theme for Landlord Blues (1987), while also having a small part in the film as attorney Sally Viscuso. She played herself in the late-'90s Pam Grier series Linc's, and at the end of the show accompanied herself on the piano for "Lift Every Voice." Most recently, she appeared in the third season of The L Word, which closed with Grier, Hendryx, and the trio BETTY singing a cover of the Hendryx track "Transformation."

In the beginning of the current decade, Hendryx was asked to appear on two of Paul Haslinger's albums. She sang lead vocals for two tracks, "Higher Purpose" and "Beginning to End", which were featured on the soundtrack for the Showtime series Sleeper Cell.

Since the breakup of Labelle, Patti, Sarah, and Nona have reunited on occasion. These reunions include Patti LaBelle's "Live In New York" video, the dance hit "Turn It Out" from the soundtrack To Wong Foo, Thanks for Everything! Julie Newmar (1995), and two television specials. In January 2006, Labelle again reunited to record "Dear Rosa," a tribute to civil rights leader Rosa Parks. Labelle also performed the theme song for the soundtrack for the film Preaching to the Choir, with Nona being the composer of the film's soundtrack. In late 2008, Labelle released their comeback album, Back to Now, and went on a successful concert tour that carried through the spring of 2009.

Speaking in April 2009 to noted UK soul/R&B writer Pete Lewis of the award-winning Blues & Soul, Hendryx discussed the background to Labelle reuniting for Back To Now: "Well, there were lots of ongoing times when we'd discussed doing it. And a lot of it was really down to the fact that the fans were DEMANDING that we did it! But, rather than just going back and doing what we'd done in the past, we did want to be able to make an album of new music before coming back out together. And it was really once we'd recorded the song 'Dear Rosa', together that Patti finally became convinced that yes, we should make a new record and then go out and tour behind it. So I'd say basically our reunion was down to two things – pressure from the fans; plus Patti hearing a sound again that she loved and hadn't heard for many years."[5]

Hendryx has authored a children's book, The Brownies.

On May 27, 2010, Hendryx performed selections from a sci-fi musical she is co-writing with Charles Randolph-Wright, Skindiver. The surprise show was at Busboys and Poets in Washington DC and sponsored by Arena Stage. Hendryx & Wright presented two late-night staged readings of Skindiver at Arena Stage in 2011.

In September 2012 Hendryx's previously download-only album, Mutatis Mutandis, received a CD release. To promote the album Hendryx appeared on the BBC's Later... with Jools Holland on 28 November 2012. In February 2013 she appeared as a special guest as part of the Captain Beefheart tribute concert, "The World of Captain Beefheart".